Nucleotide linked to protein through phosphodiester bonds has not been found in normal eucaryotic cells. Sensitive detection methodology for this posttranslational modification may be possible by the measurement of tyrosine phosphate which is produced by micrococcal nuclease treatment of nucleotidylylated protein. Quantification of tyrosine phosphate before and after enzymatic treatment can be used to detect phosphodiester linkages of nucleotide to protein. Studies on the ability of a nuclease to remove adenosine from adenylylated glutamine synthetase found that the native protein is resistant to nuclease attack while the denatured form readily undergoes deadenyosylation. This may indicate that posttranslational modification sites of proteins are protected from nonspecific enzymatic attack by tertiary or quaternary structural factors which may be involved in the control of enzymatic interconversion of proteins.